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Coming to a hard stop? Effect of tapered tocilizumab after weekly tocilizumab cessation for giant cell arteritis: A multicentre evaluation
No full textObjectives In England, there is a “hard stop” to weekly tocilizumab (qwTCZ) therapy for GCA; this is currently 12 months but was extended during the COVID-19 pandemic subject to certain criteria for GCA relapse risk. Taking advantage of variation in practice, we aimed to compare outcomes of GCA patients who tapered TCZ vs those who stopped abruptly (non-taper patients). Methods Secondary analysis of an English multicentre service evaluation of relapse after stopping qwTCZ for GCA. Time to relapse was compared between taper and non-taper patients. We examined outcomes according to whether they had been “adequate responders” during qwTCZ therapy, defined as those in remission and on ≤ 5mg prednisolone at qwTCZ cessation, without relapse whilst taking qwTCZ. Results We analysed 336 patients from 40 centres. Time to relapse after qwTCZ cessation was significantly longer in adequate responders than non-adequate responders (p = 0.0004). 17.0% (57/336) patients tapered to fortnightly TCZ after qwTCZ cessation, for a median of 6 (IQR 2–13) months. For adequate responders, time to relapse whilst taking tapered-dose TCZ was significantly longer compared with those in the non-taper group (p = 0.0231) based on a relatively small number of flares. There was no difference between the taper and non-tapered groups after tapered TCZ was stopped (p = 0.8346). In contrast, time to relapse for non-adequate responders was similar in taper-patients compared with non-taper patients (p= 0.4892). Conclusion Tapering TCZ after qwTCZ cessation delayed relapse only during the tapering period, but only in adequate responders to qwTCZ. No lasting benefit was seen after tapering ended
Evaluating the sustainability performance of sustainable, innovative, and affordable housing
Get PDFThe provision of sustainable, innovative, and affordable housing (SIAH) is a global priority, especially in rapidly urbanizing contexts. However, a comprehensive tool for assessing the sustainability performance of such housing is lacking. This study develops the SIAH Sustainability Assessment Tool (SIAH-SAT), integrating 127 validated critical success factors (CSFs) across four dimensions: economic, environmental, social, and technical. Using an exploratory mixed-method design, a Delphi process and Analytic Hierarchy Process (AHP) survey with international experts validated the CSFs and established relative sustainability weights (RSWs). The tool was applied to five diverse affordable housing cases, producing Sustainability Index (SI) scores that highlighted strengths and areas for improvement. Results demonstrate SIAH-SAT's capacity to evaluate and compare housing performance across subcategories, offering a context sensitive framework for policymakers, developers, and practitioners. By supporting evidence-based decision-making, SIAHSAT advances scientific discourse on sustainable, inclusive urban development and guides the delivery of housing aligned with global sustainability goals
Fixed versus mobile bearing medial unicompartmental knee arthroplasty with the same femoral implant design: A randomised controlled trial with a minimum of 10-year follow-up’
No full textAbstractBackground: The optimal bearing surface design for medial unicompartmental knee arthroplasty (UKA) has yet to be determined. In this randomised controlled trial from a single institution, we aimed to compare the clinical outcome, complications and joint survival of a single design femoral component medial UKA with either a fixed or mobile bearing tibial component from the same (Corin AMC, later rebranded Uniglide) implant system. Methods: This was a prospective randomised trial with patients randomised to either fixed or mobile tibial components with the Uniglide system between 2006 and 2014. The primary outcome was a patient reported outcome measure (PROM) using the Oxford Knee Score (OKS). Secondary outcomes were the American Knee Society Score (AKSS), the Western Ontario and McMaster University (WOMAC) arthritis index and the assessment of complications/reoperation. Results: There were 163 primary UKAs. With a minimum 10-year follow-up there were 101 patients with PROM scores available (53 fixed vs 48 mobile); there was no statistically significant difference between the two groups (OKS 36.9 [11.2], n = 53 vs 36.8 [9], n = 48; p = 0.990). However, regarding the early revision by 10 years, there was a statistically significant lower chance of a revision in the fixed bearing group (risk ratio was found to be 0.42 [95%CI 0.184 to 0.937; p = 0.030]). Conclusions: This study shows comparable good clinical outcomes between fixed and mobile bearing UKA with a minimum of 10-year follow-up. However, higher revision rates were demonstrated in the mobile bearing group of this randomised controlled trial over the course of 10 years
Inactivation of Listeria monocytogenes and Salmonella Typhimurium by piezoelectric cold plasma: Oxidative, structural and metabolic pathways
Get PDFCold atmospheric plasma (CAP) is an innovative, non-thermal decontamination technology with promising applications in food safety. This study investigated the antimicrobial mechanisms of CAP against the foodborne pathogens Salmonella Typhimurium and Listeria monocytogenes. CAP was applied using piezoelectric direct discharge (PDD) technology for 0, 1, 6, 9, and 15 min to simulate nonthermal decontamination conditions relevant to food processing. Antimicrobial effectiveness was evaluated using culture-based enumeration, while CAP-induced cellular damage was assessed using scanning electron microscopy (SEM), and assays measuring lipid peroxidation, reactive oxygen species accumulation, membrane permeability and malate dehydrogenase activity. Bacterial viability significantly decreased by up to 5.7 log CFU/mL after 6 min and ≤ 6.6 log CFU/mL after 9 and 15 min treatments, compared with untreated pathogens. These reductions were accompanied by corresponding increases in membrane permeability of 50%, 65%, and 94%, respectively. Culture-based enumeration confirmed reductions of ~ 4.5 log CFU/mL after 6 min and ≤ 6.5 log CFU/mL following 9 and 15 min treatments. CAP treatment for at least 6 min significantly elevated intracellular reactive oxygen species, which triggered lipid peroxidation as evidenced by elevated malondialdehyde and peroxide values. Furthermore, CAP treatment resulted in a significant reduction in malate dehydrogenase activity, indicating disruption of cellular metabolic function. SEM supported CAP-induced cellular alterations by revealing morphological damage, including porosityshrinkage and cytoplasmic leakage. Overall, PDD-generated CAP induced a multi-targeted antimicrobial effect, supporting its potential as a nonthermal decontamination method in food processing. Further research should focus on its application to a range of food matrices and its impact on quality parameters
Large spatiotemporal variability in CH4 emissions from a subtropical coastal creek affected by hydrological and biogeochemical processes in Southeast China
No full textCreeks are widespread in coastal areas and have the potential to emit substantial greenhouse gases (GHG), as they often directly receive abundant organic matter from neighboring areas. However, the high-resolution spatial variations in GHG measurement in coastal creeks are still scarce, which hampers accurate assessments of their role in global aquatic systems' GHG emission budgets. This study quantifies the seasonal and spatial variability of dissolved methane (CH4) across different seasons and calculated diffusive CH4 fluxes at a coastal creek in the Shanyutan Wetland, southeast China. Surface-water hydrographical variables and abundances of pmoA gene (for methanotroph) and mcrA gene (for methanogen) were also measured. The persistent supersaturation of surface water with CH4 relative to atmosphere levels confirms that the entire creek served as a substantial source of CH4. Greatest temporal and spatial variability in both gas concentration and diffusive fluxes were observed for CH4, which was higher in the autumn, with peaks at the head of the creek and a subsequent sharp decrease. CH4 concentrations exhibited a spatial pattern that positively aligned with levels of DOC, NH4+-N and mcrA gene abundance. In contrast, an inverse relationship was observed between CH4 distribution and gradient of salinity, DO and pmoA gene abundance. Seasonally, the variations in both CH4 concentration and efflux are driven by the combined effect of temperature, rainfall and tidewater. Overall, this study highlights that controlling terrestrial nutrient discharge is a recommended strategy to mitigate CH4 emissions from creeks
A mixed-methods study investigating the acceptability of an early acceptance and commitment therapy (ACT) intervention to aid adjustment to appearance changes after burns
No full textAppearance concerns after burns start soon after injury. However, early psychological interventions to support individuals with their changed appearance are absent. This study investigated the acceptability of an early acceptance and commitment therapy (ACT) intervention delivered by a psychological therapist either in person or virtually to help individuals adjust to changes to their appearance after burns. As a secondary objective, the potential effectiveness of ProACTive was also investigated. Using mixed-methods, 13 adults (eight women, five men) participated. Acceptability was measured by uptake rates, module completion rates and interview data. Over two-thirds of participants completed all modules. Three main themes were identified from interviews: An acceptable intervention; Valuing the therapeutic relationship; and Early support is key. Data suggested that ProACTive may be acceptable, although some inconsistencies within the data were observed. Ratings of helpfulness were positive and qualitative feedback suggested that ProACTive seemed helpful by providing space to explore and reflect on appearance changes, developing psychological flexibility and self-compassion, and preparing individuals for being around other people. Positive and negative affect significantly decreased (moderate effect sizes) but no significant changes on appearance concerns, psychological flexibility or self-compassion (small effect sizes) were revealed. ProACTive may be an acceptable early psychological intervention to support the adjustment of appearance changes after burns. Acceptability may be higher in individuals with appearance concerns and those admitted to hospital. The intervention holds promise soon after burns but further research on acceptability and effectiveness is needed
Intelligent hybrid optimization algorithms for multi-agent aerial robots path planning: review of the recent emerging trends and open research directions
No full textMulti-agent cooperation among Uncrewed Aerial Vehicles (UAVs) has become a key contributor in various application areas such as surveillance, where mission efficiency and reliability are essential. This paper aims to provide a structured work for future progress in cooperative flight by presenting a comprehensive review of the hybrid and modified optimization algorithms developed for multi-agent UAV path planning. Initially, the paper categorizes existing approaches into classical, heuristic, metaheuristic, sampling-based, control-based, and Artificial Intelligence (AI)-based frameworks, with an emphasis on their objectives, constraints, and implementation strategies. Special attention is given to metaheuristic and AI-driven techniques, which demonstrate strong adaptability and scalability in dynamic and uncertain environments. The review further examines the environmental modeling strategies, swarm architectures, and mission types, revealing the predominance of static and known environments in current research and highlighting the limited exploration of dynamic and unknown operational considerations. While performance criteria such as collision avoidance, mission duration, and cumulative path length are commonly assessed, aspects like communication constraints, task allocation, and energy efficiency remain relatively underexplored. Open research challenges and future directions are identified, including the need for real-time adaptive optimization strategies and the incorporation of more realistic agent dynamics to enhance experimental validation and practical deployment
LOTL-Hunter: Detecting multi-stage living-off-the-land attacks in cyber-physical systems using decision fusion techniques with digital twins
No full textThe integration of smart sensors and actuators in industrial environments has expanded the cyber-physical attack surface, making it increasingly difficult to distinguish anomalies caused by cyberattacks from those due to mechanical or electrical faults. This challenge is exacerbated by stealthy, multi-stage attacks leveraging Living off the Land (LOTL) techniques, which often evade conventional anomaly detection or intrusion detection systems (IDS). This study presents a Digital Twin-based testbed for safe, repeatable simulation of multi-stage cyber-physical attacks targeting Cyber-Physical Systems (CPS) and Industrial Control Systems (ICS). We propose a two-level decision fusion method that aggregates and aligns anomalies across network, process, and host domains in synchronized 1-minute intervals. The first-level fusion improves OT-layer detection by applying confidence-aware decision logic to outputs combined from (a) a supervised deep learning model (LSTM-FCN) for process anomalies, (b) an unsupervised model (Isolation Forest) for OPC UA network anomalies, and (c) process alarm signals. The second-level fusion integrates these results with host-based anomalies, computed through point-based scoring of Wazuh alerts, to provide comprehensive IT/OT situational awareness. Experimental results demonstrate improved detection of stealthy, multi-stage APT attack behaviours. Additionally, Large Language Models (LLM) provide summarization of the integrated IT/OT anomaly logs into human-readable insights, enhancing interpretability and supporting cyber threat hunting
Diagnostic accuracy of a novel point of care high‐sensitivity troponin assay in the prehospital environment
No full textObjective To evaluate the diagnostic accuracy of a novel point of care (POC) high‐sensitivity troponin (hs‐cTn) assay, used alone or incorporated within validated decision aids, for acute myocardial infarction (AMI) in the prehospital setting. Methods A pre‐specified secondary analysis of the Prehospital Evaluation of Sensitive Troponin (PRESTO) prospective diagnostic accuracy study, conducted in four ambulance services and 12 Emergency Departments (EDs; February 2019–March 2020). Paramedics included consenting adults with suspected AMI and no other reason for conveyance. Clinical data and venous blood were collected at the scene, and samples conveyed to hospital with participants. Plasma samples were later analyzed for hs‐cTn using a novel POC hs‐cTn assay (Abbott Point of Care i‐STAT hs‐TnI). The target condition was an adjudicated index diagnosis of type 1 AMI. Results Of 817 consenting participants, 704 were eligible for inclusion in this analysis, with type 1 AMI occurring in 89 (12.6%). At the limit of detection (< 2 ng/L), POC hs‐cTn had 100.0% sensitivity (95% CI 95 9%–100.0%) but only 4.6% specificity (95% CI 3.1%–6.5%). A Troponin‐only Manchester Acute Coronary Syndromes (T‐MACS) very‐low risk outcome identified 134 (19.7%) patients for non‐conveyance with 98.9% sensitivity (95% CI 94.9%–100.0%), 99.3% negative predictive value (NPV, 95% CI 95.0%–99.9%), and 22.5% specificity (95% CI 19.2%–26.1%). A low‐risk modified HEART score identified 150 (22.0%) patients with 93.2% sensitivity (95% CI 85.8%–97.5%), 96.0% NPV (91.6%–98.1%), and 24.3% specificity (95% CI 20.9%–27.9%). In an exploratory analysis, hs‐cTn < 5 ng/L identified 295 (41.9%) patients with 98.9% sensitivity (93.9%–100.0%), 99.7% NPV (97.7%–100.0%), and 47.8% specificity (95% CI 43.8%–51.8%). Conclusions This novel POC hs‐cTn assay achieves high sensitivity and NPV when used alongside the T‐MACS decision aid, but efficiency may be greater at a 5 ng/L threshold without requiring any decision aid. Trial Registration ClinicalTrials.gov identifier: NCT0356105
Connecting evidence with decision-making in adult social care: A cross-sectional staff survey
Get PDFSummaryFor adult social care organizations faced with growing challenges, an increasingly important issue is how best to make use of relevant research. This article reports on a survey that sought to assess the views, experiences, and use of research among adult social care staff in three neighboring local authorities in England.FindingsIn total, 250 staff (30% response rate) across all grades and areas of practice responded to the survey. Staff expressed positive views about the role of research in practice and 36% of respondents could think of changes to their practice that were informed by research findings. Staff with personal experience of doing research, on more senior grades, and in receipt of relevant training reported more positive views, knowledge, skills, and application of research. Elements of research engagement were reported more frequently by occupational therapist staff compared to those in social work. There were no significant differences based upon duration of service or recency of professional qualification. Staff trained in literature searching and critical appraisal were generally not confident to apply their learning. Inadequate time was a leading barrier to research engagement.ApplicationsThis study highlights the need for an organization-wide perspective on promoting greater use of research evidence in adult social care decision-making. From this stance, our research indicates the importance of attending to the interests and capacities of diverse staff groups alongside a focus on specific staff-informed opportunities and leverage points through which to disseminate the use of research evidence in complex organizations